The broad aim of this grant is to expand the material collected by the Australian Breast Cancer Family Study (ABCFS) between 1996 and 2000 on 1,5000 families as part of the CFRBCS, in terms of pathology, biospecimens, clinical data and epidemiology. The specific aims are for this resource to contribute to the 13 Scientific Modules of this competitive UO1 grant application. This includes a 5 year Systematic Follow-up Study of all 20,000 consenting individuals (8,000 affected) recruited into the CFBRCS, so as to form a prospective cohort study for cancer families. It also includes a study of cases and 750 controls in both Australia and Canada, and replication of positive findings sought by within-family analyses of population-based resources from those two sites, and from Northern California. These two modules are included in this application. It is proposed that an Australian Breast Cancer Family Registry (ABCFR) be created by combining the above material with data collected in 1992- 1995 by the ABCFS on 466 case and 408 control families by the ABCFS using local funds, and by adding a new consortium, the Kathleen Cunningham Foundation Consortium for Research in Familial Breast Cancer (KconFab), also locally funded. Funding is sought for follow-up of an anticipated 400 families, and for testing for mutations in BRCA1 and BRCA2 in 500 KconFab families. As well as being coordinators on the two modules above, the PIs of the ABCFS have a major role on other modules, including the Prognosis and Pathology Characteristics of Heritable Breast Cancer, Estrogen Gene Variants and Breast Cancer, Penetrance and Prevalence of BRCA1/BRCA2 Mutations in the CFRBCS and Identification of Novel Genes Involved in Breast Cancer Susceptibility. Funding is sought for the contribution to these and other modules of data, DNA and administration of questionnaires. This Australian Registry will make a major contribution to the CFRBC's efforts to elucidate the genetic and environmental causes of breast cancer, and translate this into benefits for women at risk of, or affected by, breast cancer.